Epidural clonidine analgesia following surgery: phase I.

Epidurally administered clonidine has been reported to produce postoperative analgesia. To assess the efficacy, safety, and appropriate dose of epidural clonidine for postoperative analgesia, clonidine (range, 100-900 micrograms in 100-micrograms increments) was injected in 22 patients following abdominal surgery or total knee arthroplasty (TKA). Clonidine produced analgesia, as measured by change in verbal pain scores and supplemental iv morphine usage. The largest doses examined (700-900 micrograms) produced complete pain relief for 5.0 +/- 0.8 h (mean +/- SEM; range 2-11 h), without other sensory or motor blockade. Clonidine also produced dose dependent decreases in blood pressure, being less following small (100-300 micrograms) and large (700-900 micrograms) doses than following intermediate (400-600 micrograms) doses. Six patients required iv ephedrine for treatment of blood pressure decrease of greater than 30%. Clonidine decreased heart rate 10-30% and produced transient sedation. Oxyhemoglobin saturation, serum glucose, and arterial blood gas tensions were not altered by clonidine, whereas there was a small (28%) dose-independent decrease in serum cortisol following clonidine injection. Clonidine was absorbed in a dose-dependent manner into the systemic circulation, with plasma concentrations 0.1-3.3 ng/ml 1 h following injection. These results suggest that hemodynamic depression and short-lasting analgesia may limit the usefulness of bolus epidural clonidine analgesia in the postoperative setting.